DESCRIPTION: The aim of this research is to understand the mechanism by which poliovirus directs the efficient production of its own proteins while effectively inhibiting the synthesis of host cell proteins. Previous studies from this, as well as other investigator's laboratories have demonstrated that the synthesis of a viral proteinase to 2A induces a specific cleavage of the largest polypeptide subunit P220 of the cellular translation initiation factor, eIF-4F which mediates the binding of capped cellular mRNAs to the ribosome. The synthesis of viral proteins then occurs under conditions where translation of cellular mRNA is inhibited. Viral mRNA binds to ribosome by unique capped independent mechanism that relies on the interaction of a spatial array of structural domains in the 5' noncoding region with a set of cellular proteins that mediate ribosome binding at an internal, rather than 5' end site. In this revised proposal, the investigator wishes to further analyze the 5' NCR of poliovirus and proposes the following specific aims. To analyze the structure and function of domain IV of the poliovirus 5' NCR. To evaluate unwinding of the 5' NCR during translation initiation. To identify the mechanism of enhancement of IRES-driven translation by 2A. To compare poliovirus and hepatitis A virus IRES function.